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本文引用的文献

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Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial.普伐他汀用于预防高危孕妇先兆子痫的安全性和药代动力学:一项前瞻性随机对照试验
Am J Obstet Gynecol. 2016 Jun;214(6):720.e1-720.e17. doi: 10.1016/j.ajog.2015.12.038. Epub 2015 Dec 23.
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Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia.普伐他汀对人胎盘、内皮细胞及重度子痫前期患者的影响。
Hypertension. 2015 Sep;66(3):687-97; discussion 445. doi: 10.1161/HYPERTENSIONAHA.115.05445. Epub 2015 Jul 27.
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Management of preeclampsia.子痫前期的管理。
Pregnancy Hypertens. 2014 Jul;4(3):246-7. doi: 10.1016/j.preghy.2014.04.021. Epub 2014 Jul 9.
4
Immunotherapy in antiphospholipid syndrome.抗磷脂综合征中的免疫疗法。
Int Immunopharmacol. 2015 Aug;27(2):200-8. doi: 10.1016/j.intimp.2015.06.006. Epub 2015 Jun 15.
5
Pravastatin to prevent recurrent fetal death in massive perivillous fibrin deposition of the placenta (MPFD).普伐他汀预防胎盘大量绒毛周围纤维蛋白沉积(MPFD)所致复发性胎儿死亡。
J Matern Fetal Neonatal Med. 2016 Mar;29(6):855-62. doi: 10.3109/14767058.2015.1022864. Epub 2015 Apr 20.
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Statins and congenital malformations: cohort study.他汀类药物与先天性畸形:队列研究
BMJ. 2015 Mar 17;350:h1035. doi: 10.1136/bmj.h1035.
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Diagnosis and management of non-criteria obstetric antiphospholipid syndrome.非标准型产科抗磷脂综合征的诊断与管理
Thromb Haemost. 2015 Jan;113(1):13-9. doi: 10.1160/TH14-05-0416. Epub 2014 Oct 16.
8
Long-term maternal morbidity and mortality associated with ischemic placental disease.与胎盘缺血性疾病相关的长期母体发病率和死亡率。
Semin Perinatol. 2014 Apr;38(3):146-50. doi: 10.1053/j.semperi.2014.03.003.
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Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health.产妇并发症和围产儿死亡率:世界卫生组织产妇和新生儿健康多国调查结果。
BJOG. 2014 Mar;121 Suppl 1:76-88. doi: 10.1111/1471-0528.12633.
10
Clinical improvement and successful pregnancy in a preeclamptic patient with antiphospholipid syndrome treated with pravastatin.用普伐他汀治疗的抗磷脂综合征先兆子痫患者的临床改善及成功妊娠
Hypertension. 2014 May;63(5):e118-9. doi: 10.1161/HYPERTENSIONAHA.114.03115. Epub 2014 Mar 3.

普伐他汀可改善抗血栓治疗难治的产科抗磷脂综合征患者的妊娠结局。

Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy.

作者信息

Lefkou Eleftheria, Mamopoulos Apostolos, Dagklis Themistoklis, Vosnakis Christos, Rousso David, Girardi Guillermina

出版信息

J Clin Invest. 2016 Aug 1;126(8):2933-40. doi: 10.1172/JCI86957. Epub 2016 Jul 25.

DOI:10.1172/JCI86957
PMID:27454295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4966313/
Abstract

BACKGROUND

Administration of conventional antithrombotic treatment (low-dose aspirin plus low-molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency-associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes.

METHODS

We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated.

RESULTS

In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients.

CONCLUSION

The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.

摘要

背景

对于产科抗磷脂综合征(APS),采用传统抗血栓治疗(小剂量阿司匹林加低分子肝素[LDA+LMWH])并不能预防20%的患者发生危及生命的胎盘功能不全相关并发症,如子痫前期(PE)和胎儿生长受限(IUGR)。他汀类药物已被证明可改善PE和APS小鼠模型的妊娠结局,这可能与其对内皮的保护作用有关。在此,我们研究了普伐他汀在LDA+LMWH治疗无效且妊娠不良结局风险增加的APS患者中的应用。

方法

我们研究了21例在LDA+LMWH治疗期间发生PE和/或IUGR的APS孕妇。10例患者组成的对照组仅接受LDA+LMWH治疗。11例患者在发生PE和/或IUGR时,除接受LDA+LMWH治疗外,还接受普伐他汀(20mg/d)治疗。评估子宫胎盘血流动力学、PE特征(高血压和蛋白尿)的进展以及胎儿/新生儿结局。

结果

对照组所有分娩均为早产,11例新生儿中仅6例存活。在6例存活的新生儿中,3例发育异常。接受普伐他汀和LDA+LMWH联合治疗的患者胎盘血流增加,PE特征有所改善。这些有益效果在普伐他汀治疗开始后10天就已观察到。普伐他汀与LDA+LMWH联合治疗还使所有患者的活产接近足月。

结论

本研究表明,普伐他汀在PE或IUGR发生时开始服用直至妊娠结束,可能改善难治性产科APS女性的妊娠结局。